This proposal is for 5-year renewal of the NIMH Research Scientist Award of Dr. D.F. Kripke at UCSD. In this research plan, the investigator summarizes the major funded projects he is currently completing, as well as additional areas. The major focus of the proposal is the role of circadian pacemakers and melatonin in affective disorders. In the coming 5 years, the P.I. plans to develop a new Circadian Pacemaker Laboratory for research on the human circadian system. Projects to be carried out include, 1) a study of effects of bright light in a shiftwork model to examine circadian pacemaker dynamics, explore actions of phototherapy, and study applied benefits of phototherapy in shiftworkers; 2) a study of how varying profiles of illumination intensity and duration affect photoperiodic control of melatonin and other circadian rhythms; 3) a study of chronopharmacologic effects of anti-depressant and anti- manic drugs; 4) two studies of how variation in population illumination exposure are related to affective symptoms, sleep disorders, and reproductive endocrinology. An additional focus is the mental health implication of sleep-related respiratory disturbances (eg., sleep apnea). Two funded studies will explore the prevalence of sleep-related respiratory disturbances in a population sample age 40-64 and examine the morbidity and mortality risks associated with sleep-related respiratory disorders.